OBJECTIVE: We endeavored to introduce a novel scoring system (Lumbar Functional Index, LFI) capable of evaluating lumbar function in pelvic bone sarcoma patients who underwent surgical resection and spinal pelvic fixation, while simultaneously identifying the incidence, outcomes, and risk factors of lumbar function impairment among these populations.
METHODS: A cohort of 304 primary bone sarcoma patients were recruited. The LFI was created based on the Oswestry Dysfunction Index (ODI) and Japanese Orthopaedic Association (JOA) scores. Lumbar function impairment was defined as LFI score ≥ 18 points, which was identified as high LFI. Demographic data, clinical characteristics, and oncological outcomes were analyzed.
RESULTS: The cohort included chondrosarcoma (39.8%), osteosarcoma (29.9%), Ewing sarcoma (8.6%), bone-derived undifferentiated pleomorphic sarcoma (7.2%), giant cell tumor of bone (7.2%), chordoma (2.3%), and other bone sarcomas (5.0%). The LFI score exhibited significant negative correlation with common scoring systems of bone sarcoma. The incidence of high LFI was 23.0%. Patients with high LFI demonstrated a higher prevalence of type I + II + III + IV pelvic tumor, more sacrificed nerve roots and bilateral lumbar spine fixation during surgery, while lower percentage of R0 resection and local control of pelvic tumor. Decreased median overall survival (30 vs. 52 months, p < 0.001) and recurrence-free survival (14 vs. 24 months, p < 0.001) time were observed in these patients. Type I + II + III + IV pelvic tumor and sacrificed nerve roots≥2 were identified as risk factors for high LFI, while R0 resection and local control were identified as protective factors.
CONCLUSIONS: The LFI scoring system exhibited a significant negative correlation to current scoring systems. High LFI patients had worse prognosis and distinct characteristics. The risk factors of high LFI included type I + II + III + IV pelvic tumor and sacrificed nerve roots≥2, and the protective factors included R0 resection and local control.

OBJECTIVE: Currently, there is a lack of good clinical tools for evaluating the effect of chemotherapy preoperatively on primary high-grade bone sarcomas. Our goal was to investigate the predictive value of the clinical findings and establish a scoring system to predict chemotherapy response.
METHODS: We conducted a retrospective multicenter cohort study and reviewed 322 patients with primary high-grade bone sarcomas. Patients who routinely received neoadjuvant chemotherapy and underwent primary tumor resection with an assessment of tumor necrosis rate (TNR) were enrolled in this study. The medical records of patients were collected from November 1, 2011, to March 1, 2018, at Peking University People\'s Hospital (PKUPH) and Peking University Shougang Hospital (PKUSH). The mean age of the patients was 16.2 years (range 3-52 years), of whom 65.5% were male. The clinical data collected before and after neoadjuvant chemotherapy included the degree of pain, laboratory inspection, X-ray, CT, contrast-enhanced magnetic resonance (MR), and positron emission tomography-computed tomography (PET-CT). Several machine learning models, including logistic regression, decision trees, support vector machines, and neural networks, were used to classify the chemotherapy responses. Area under the curve (AUC) of the scoring system to predict chemotherapy response is the primary outcome measure.
RESULTS: For patients without events, a minimum follow-up of 24 months was achieved. The median follow-up time was 43.3 months, and it ranged from 24 to 84 months. The 5 years progression-free survival (PFS) of the included patients was 54.1%. The 5 years PFS rate was 39.7% for poor responders and 74.9% for good responders. Features such as longest diameter reduction ratio (up to three points), clear bone boundary formation (up to two points), tumor necrosis measured by magnetic resonance (up to two points), maximum standard uptake value (SUVmax ) decrease (up to three points), and significant alkaline phosphatase decrease (up to 1 point) were identified as significant predictors of good histological response and constituted the scoring system. A score ≥4 predicts a good response to chemotherapy. The scoring system based on the above factors performed well, achieving an AUC of 0.893. For nonmeasurable lesions (classified by the revised Response Evaluation Criteria in Solid Tumors [RECIST 1.1]), the AUC was 0.901.
CONCLUSIONS: We first devised a well-performing comprehensive scoring system to predict the response to neoadjuvant chemotherapy in primary high-grade bone sarcomas.

OBJECTIVE: Socioeconomic and racial disparities have been recognized as impacting the care of patients with cancer, however there are a lack of data examining the impact of these disparities on patients with bone sarcoma. The purpose of this study was to examine socioeconomic and racial disparities that impact the oncological outcomes of patients with bone sarcoma.
METHODS: We reviewed 4,739 patients diagnosed with primary bone sarcomas from the Surveillance, Epidemiology and End Results (SEER) registry between 2007 and 2015. We examined the impact of race and insurance status associated with the presence of metastatic disease at diagnosis, treatment outcome, and overall survival (OS).
RESULTS: Patients with Medicaid (odds ratio (OR) 1.41; 95% confidence interval (CI) 1.15 to 1.72) and uninsured patients (OR 1.90; 95% CI 1.26 to 2.86) had higher risks of metastatic disease at diagnosis compared to patients with health insurance. Compared to White patients, Black (OR 0.63, 95% CI 0.47 to 0.85) and Asian/Pacific Islander (OR 0.65, 95% CI 0.46 to 0.91) were less likely to undergo surgery. In addition, Black patients were less likely to receive chemotherapy (OR 0.67, 95% CI 0.49 to 0.91) compared to White patients. In patients with chondrosarcoma, those with Medicaid had worse OS compared to patients with insurance (hazard ratio (HR) 1.65, 95% CI 1.06 to 2.56).
CONCLUSIONS: In patients with a bone sarcoma, the cancer stage at diagnosis varied based on insurance status, and racial disparities were identified in treatment. Further studies are needed to identify modifiable factors which can mitigate socioeconomic and racial disparities found in patients with bone sarcomas. Cite this article: Bone Joint Res 2022;11(5):278-291.

Bone sarcomas are rare cancers accompanied by metastatic disease, mainly including osteosarcoma, Ewing sarcoma and chondrosarcoma. Extracellular vesicles (EVs) are membrane vesicles released by cells in the extracellular matrix, which carry important signal molecules, can stably and widely present in various body fluids, such as plasma, saliva and scalp fluid, spinal cord, breast milk, and urine liquid. EVs can transport almost all types of biologically active molecules (DNA, mRNA, microRNA (miRNA), proteins, metabolites, and even pharmacological compounds). In this review, we summarized the basic biological characteristics of EVs and focused on their application in bone sarcomas. EVs can be use as biomarker vehicles for diagnosis and prognosis in bone sarcomas. The role of EVs in bone sarcoma has been analyzed point-by-point. In the microenvironment of bone sarcoma, bone sarcoma cells, mesenchymal stem cells, immune cells, fibroblasts, osteoclasts, osteoblasts, and endothelial cells coexist and interact with each other. EVs play an important role in the communication between cells. Based on multiple functions in bone sarcoma, this review provides new ideas for the discovery of new therapeutic targets and new diagnostic analysis.

Bone sarcomas such as osteosarcoma and chondrosarcoma are frequently refractory to conventional chemotherapy and radiotherapy that exhibit poor prognosis. The Wnt signaling are evolutionarily conserved and implicated in cell proliferation and sarcomagenesis. However, the potential role of the Wnt signaling in bone sarcomas is still unclear. Here we demonstrate aberrant activation of Wnt/β-catenin signaling in bone sarcoma cells, involving an autocrine Wnt signaling loop with upregulation of specific Wnt ligands and receptors. Activation of Wnt/β-catenin signaling with Wnt3a or GSK-3β inhibitor drives the proliferation of bone sarcoma cells, whereas downregulation of activated Wnt signaling with dnTCF4 or siLEF1 suppresses bone sarcoma proliferation and induces cell cycle arrest. Taken together, our findings establish the evidence that aberrant activation of Wnt/β-catenin pathway involving an autocrine Wnt singaling drives the proliferation of bone sarcoma cells, and identify the autocrine activation of the Wnt/β-catenin signaling as a potential novel therapeutic target for bone sarcomas.